炎症是机体对内外环境有害刺激产生的以防御为主的基本病理过程，但过强以及持续时间过长的炎症均可导致非特异性组织损伤，因此炎症反应的强度和时间在机体需受到严密调控。炎症消退（inflammation resolution）是炎症反应主动诱导的，多机制和多分子参与炎症生理阶段，是炎症自身反馈性调控机制，起着终止炎症反应作用，是炎症自限的主要原因；其功能不足导致炎症慢性化，与多种慢性炎症性疾病密切相关；促炎症消退分子抗炎机制不同于传统药物，为抗炎药物研制新方向，因此发现新促炎症消退分子并阐明其机理具重要意义。巨噬细胞吞噬凋亡细胞诱导的炎症抑制和组织修复是促炎症消退的核心机制，张志仁教授课题组前期研究发现了促红细胞生成素（EPO）在生理条件下促巨噬细胞吞噬清除凋亡细胞作用（Immunity 2016, 44, 287–302）。在此基础上，张志仁教授等发现炎症条件下，浸润吞噬细胞氧呼吸爆发可导致局部低氧而诱导局部EPO和巨噬细胞EPOR升高；进一步采用Lyz2-Cre-Eporloxp/loxp 小鼠，他们发现巨噬细胞EPOR通路在促进炎症消退中起着重要作用，其机制与促进凋亡细胞吞噬清除及促进巨噬细胞淋巴结回流相关；并且EPO治疗可显著促进慢性炎症的消退。
        该研究揭示了一条新的炎症反馈调控通路，即“氧呼吸爆发-低氧-巨噬细胞EPOR通路激活-炎症消退”；发现EPO为促炎症消退新分子，为调控炎症消退提供了新靶点，为临床上炎症相关疾病的治疗提供了新靶点。

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An essential role of erythropoietin in promoting inflammation resolution discovered by Zhiren Zhang ａnd Yuzhang Wu Groups

Prof. Zhiren Zhang, Yuzhang Wu ａnd colleagues, Institute of Immunology，PLA, Third Military Medical University, have reported that macrophage erythropoeitin signaling is important for promoting inflammation resolution. This report entitled “Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution” was published on Nat. Commun. 7:12177 doi: 10.1038/ncomms12177 (2016).

Acute inflammation is a physiological response to tissue damage or infection that is self-limited ａnd generally beneficial to the host; however, ungoverned inflammation is highly detrimental ａnd is a unifying basis of many widely occurring diseases, such as atherosclerosis,obesity ａnd cancer. Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental ａnd of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia ａnd macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice ａnd chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, ａnd exogenous erythropoietin enhances this resolution in WT ａnd CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris ａnd enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions.

Article：Luo B, Wang J, Liu Z, Shen Z, Shi R, Liu YQ, Liu Y, Jiang M, Wu Y*, Zhang Z*. Phagocyte respiratory burst activates macrophage eryth

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